Navigation Links
Origin of inherited pain disorder pinpointed

The genetic basis for a rare inherited disorder that causes severe burning pain with no warning has been pinpointed by researchers. They found that paroxysmal extreme pain disorder (PEPD) is caused by specific mutations in porelike sodium channels in peripheral nerve cells—a discovery that they said emphasizes the role of such channel disorders in inflammatory pain. Such findings of abnormal function in disease also provide insights into the normal function of such channels, they said.

R. Mark Gardiner, of University College London, and his colleagues published their findings in the December 7, 2006, issue of the journal Neuron, published by Cell Press.

So-called "voltage-gated sodium channels" are central to the neuron's ability to propagate a nerve impulse. In response to voltage changes in a nerve cell caused by a nerve impulse, these channels snap open, allowing sodium to flow across the cell membrane, further propagating the nerve impulse. Rapid, precise activation and inactivation is key to their normal operation.

In their studies, the researchers sought to understand the basis of PEPD, which is characterized by abrupt paroxysms of pain in the rectum, eye, and jaw. They first performed a detailed genetic comparison of affected and unaffected members of one large family that showed inheritance of the disease. That analysis revealed that mutations that compromise the gene for a component of one particular sodium channel, called SCN9A, were the likely culprit. Further analysis of the gene in 11 affected families and two sporadic cases, indeed, revealed that mutations in SCN9A are responsible for the disease in at least two-thirds of PEPD cases.

Analysis of these mutations revealed that they all disrupted the ability of the sodium channel to rapidly snap shut, prolonging activation of the peripheral nerves in which the channels functioned. What's more, the researchers found, the drug carbamazepine—known to be effective in PEPD—act s to correct this abnormality in cultures of neurons.

The researchers also compared PEPD with another inherited pain disorder, primary erythermalgia (PE) that is not alleviated by carbamazepine. PE is also caused by mutations in SCN9A and is characterized by pain in the extremities triggered by exercise or temperature change. In contrast to PEPD, which is caused by mutations that disrupt inactivation the sodium channel, PE arises from mutations that lower its activation threshold.

The researchers concluded that their findings "further emphasize the critical role of [this sodium channel] in human inflammatory pain and explain the differential drug sensitivity of PEPD and PE."


'"/>

Source:Cell Press


Related biology news :

1. International Team Determines Geographic Origin of Leprosy
2. New Look at DNA Hints at Origin of UV Damage
3. Stem Cells Found In Cerebellum; Possible Cell of Origin for Childhood Brain Tumors
4. Researchers Discover Ancient Origins Of Tuberculosis-causing Bacteria
5. Genetic therapy reverses nervous system damage in animal model of inherited human disease
6. Tendency to hair loss inherited from the mother
7. Gene therapy cures inherited liver disease in rats
8. Cell therapy slows progression of an inherited neurological disease; Improves motor skills in mice
9. Early-stage immune system control of HIV may depend on inherited factors
10. Association of herpesvirus with lung disorder questioned
11. Newly discovered virus linked to childhood lung disorders and Kawasaki disease
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:2/1/2016)... , February 1, 2016 ... advancements to drive global touchfree intuitive gesture control market ... --> Rising sales of consumer electronics coupled with ... control market size through 2020 ... electronics coupled with new technological advancements to drive global ...
(Date:1/25/2016)... --  Unisys Corporation (NYSE: UIS ) today announced the ... Airport, New York City , to help ... enter the United States using passports that ... testing of the system at Dulles last year. The system ... January 2016. --> pilot testing of the system ...
(Date:1/20/2016)... Jan. 20, 2016 A market that just ... benefit from the explosion in genomics knowledge. Learn all ... Research. A range of dynamic trends are pushing market ... personalized medicine - pharmacogenomics - pathogen evolution - next ... markets - greater understanding of the role of genetic ...
Breaking Biology News(10 mins):
(Date:2/11/2016)... , Germany and ... -- QGEN ; Frankfurt Prime Standard: QIA) ... QIAseq Targeted RNA Panels for gene expression profiling, expanding ... sequencing (NGS). The panels enable researchers to select from ... fold changes and discover interactions between genes, cellular phenotypes ...
(Date:2/11/2016)... ... February 11, 2016 , ... ... cutting-edge information focused on the development and manufacture of biopharmaceuticals and therapeutics, ... sponsor of the 2016 BioProcess International Awards – Recognizing Excellence in the ...
(Date:2/11/2016)... Buffalo, New York (PRWEB) , ... February 11, ... ... and analytical instruments for more than 150 years, continues today to pursue the ... to its line of analytical instruments: the AR9 Refractometer and the AR5 Refractometer. ...
(Date:2/10/2016)... 10, 2016 Early-career researchers from ... Peru , Uganda and Yemen ... health and nutrition   Indonesia , ... and Yemen are being honored for their ... are also celebrated for mentoring young women scientists who are pursuing careers ...
Breaking Biology Technology: